Interactions between a symmetrical minor groove binding compound and dna oligonucleotides:1h and19f nmr studies

Andrew H. Wang, Sylvain Cottens, Peter B. Dervan, James P. Yesinowski, Gijs A. Van Der Marel, Jacques H. Van Boom

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12 引文 斯高帕斯(Scopus)


Highresolution NMR techniques (proton and19F) have been used to study the interactions between several DNA oligonucleotides with varying length of ATbase pairs and the synthetic pyrrole-containing compound (P1 -F4S-P1), which has properties similar to the DNA minor groove binding drug distamycin A When this two-fold symmetrical DNA binding molecule is added to the self-complementary DNA oligomers, the resulting complex exhibits an NMR spectrum without any doubling of individual resonances, consistent with a two-fold symmetry of the complex. This is in contrast to all other complexes studied so far. The minimum length of an AT stretch for specific ligand binding is judged to be greater than 4 base pairs. Intermolecular proton nuclear Overhauser effects between the ligand molecule and a DNA dodecamer d(CGCAAATTTGCG) provide evidence that P1-F4S-P1 binds DNA in the minor groove and interacts with the middle AT base pairs. The presence of a specific interaction between P1-F4S-P1 and DNA is conclusively demonstrated by19F NMR studies, in which four previously chemically equivalent fluorine nuclei in the free molecule become two nonequivalent pairs (yielding an AB quartet pattern) upon the binding of P1-F4S-P1 to DNA duplex. A sequence-dependent binding behavior of P1 -F4S-P1 is evident by comparing the19F NMR spectra of the complexes between P1 -F4S-P1 and two different but related DNA dodecamers, d(CGCAAATTTGCG) and d(CGCTTTAAAGCG). P1-F4S-P1 binds more strongly to the former dodecamer with an association constant of 1 × 103 M-1.

頁(從 - 到)101-118
期刊Journal of Biomolecular Structure and Dynamics
出版狀態已發佈 - 8月 1989

ASJC Scopus subject areas

  • 結構生物學
  • 分子生物學


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